新型2,4-二取代-7-甲基-1,1,3-三氧代-2,4-二氢-吡唑并-[4,5-e][1,2]噻二嗪的合成及抗HIV活性评价
Synthesis and anti-HIV activity evaluation of novel 2,4-disubstituted 7-methyl-1,1,3-trioxo-2,4-dihydro-pyrazolo-[4,5-e][1,2]thiadiazines.
作者信息
Liu Xin-yong, Yan Ren-zhang, Wang Yan, Zhan Peng, De Clercq Erik, Pannecouque Christophe, Witvrouw Myriam, Molina Maria Teresa, Vega Salvador
机构信息
Institute of Medicinal Chemistry, School of Pharmaceutical Sciences, Shandong University, Jinan, PR China.
出版信息
Arch Pharm (Weinheim). 2008 Apr;341(4):216-22. doi: 10.1002/ardp.200700216.
A series of novel 2,4-disubstituted 7-methyl-1,1,3-trioxo-2,4-dihydro-pyrazolo[4,5-e] [1,2,4]thiadiazines (PTDs) was synthesized, structurally confirmed by spectral analysis, and evaluated for their anti-HIV activities by inhibition of HIV-induced cytopathogenicity in MT-4 cell culture. The results showed that some compounds exhibited inhibitory activity specifically against HIV-2 replication. The most active HIV-2 inhibitor was compound 7i (R1 = benzyl, R2 = 4-t-butyl-benzyl) with an EC50 value of 18.7 microM and SI=15, which may provide a useful lead for further molecular optimization.
合成了一系列新型的2,4-二取代-7-甲基-1,1,3-三氧代-2,4-二氢-吡唑并[4,5-e][1,2,4]噻二嗪（PTDs），通过光谱分析对其结构进行了确认，并通过在MT-4细胞培养中抑制HIV诱导的细胞病变效应来评估它们的抗HIV活性。结果表明，一些化合物对HIV-2复制表现出特异性抑制活性。活性最高的HIV-2抑制剂是化合物7i（R1 = 苄基，R2 = 4-叔丁基苄基），其EC50值为18.7 microM，SI = 15，这可能为进一步的分子优化提供有用的先导化合物。
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